This project aims at the analysis of various cell surface properties of metastatic cells which control tumor cell dissemination via immune and nonimmune interactions between the tumor cell and the tumor-bearing organism. We study the expression of MHC gene products on metastatic as distinct from nonmetastatic clones, and their function in controlling the metastatic phenotype. Thus, analyzing a large number of clones of the metastatic 3LL Lewis lung carcinoma (of H-2b origin), we found that the lower the H-2Kb/H-2Db ratio on tumor cell surface, the higher theirmetastatic competence. Interferon alpha and beta and retinoic acid, applied in vitro, caused a net increase in the cell surface expression of H-2Db glycoproteins. This was associated with a significant increase of the metastatic properties. To achieve the reduction or abolishment of the metastatic properties, H-2K gene transfection was attempted. Functional studies indicated that clones of high H-2K/H-2D ratio (nonmetastatic) are significantly more immunogenic and more susceptible to immune responses than clones of low H-2K/H-2D ratio (metastatic). T-cell mediated immune responses participate significantly in controlling the expression of the metastatic phenotype. Gene cloning of the MHC of the tumor cells is carried out to investigate the molecular basis of suppression in H-2K expression in metastatic clones. A similar approach is applied to a metastatic model of a heterozygous (H-2b x H-2k)F1 origin, the T10 sarcoma. Both metastatic and nonmetastatic clones do not express the H-2K of either haplotype. Immunoselection experiments indicated that the metastatic phenotype is determined just by the expression of the H-2Dk. Nonmetastatic clones, which differ from the metastatic only in H-2 expression, are significantly more immunogenic. Induction of H-2K expression reduced the metastatic competence while increasing immunogenicity. The molecular basis of the differential structure, expression, and function of class 1 antigens on metastatic tumors is investigated. This is carried out in parallel with studies on oncogenes in metastatic and nonmetastatic clones. Our previous studies indicated that the excision of the local tumor was followed by acceleration of metastatic growth. We subsequently observed that general anesthesia enhanced the postsurgical acceleration of metastasis. Two anesthetic drugs used in our experiments were found to suppress NK activity. Inducers of NK activity prevented the postsurgical acceleration of metastases caused by anesthetics. (IB)